Putative role for EPC-1/PEDF in the G0 growth arrest of human diploid fibroblasts

Robert J. Pignolo, Mary Kay Francis, Mitch O. Rotenberg, Vincent J. Cristofalo

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

EPC-1/PEDF expression is closely associated with reversible growth arrest in normal human diploid fibroblast-like (HDF) cells and is diminished with proliferative senescence in vitro. EPC-1 expression in HDF cells is induced under conditions of density-dependent contact inhibition and growth factor deprivation. Antiserum generated against EPC-1 recognizes a secreted protein of approximately 50 kDa from medium conditioned by early passage HDF cells, but not from senescent cells. The addition of EPC-1 antiserum to early population doubling level (PDL) cultures near the plateau phase of growth significantly increases the number of cells entering DNA synthesis. Affinity purified EPC-1 antibodies alone enhance the ability of near plateau-phase early PDL WI-38 cells to synthesize DNA by as much as threefold. Further, the addition of recombinant EPC-1 (rEPC-1) to logarithmically growing cells resulted in a marked decrease in the ability of these cells to enter DNA synthesis. We also demonstrate the loss of EPC-1 expression in WI-38 and IMR-90 HDF cell lines with both senescence and simian virus 40 (SV40) transformation. The loss of EPC-1 expression with SV40 transformation occurs at the level of steady-state mRNA and protein accumulation with genomic EPC-1 sequences grossly intact. Taken together, these results suggest that EPC-1 may play a role in the entry of early passage fibroblasts into a G0 state or the maintenance of such a state once reached.

Original languageEnglish (US)
Pages (from-to)12-20
Number of pages9
JournalJournal of Cellular Physiology
Volume195
Issue number1
DOIs
StatePublished - Apr 1 2003

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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